The broad, long term objectives of this program are the early detection of the presence of glaucoma and evaluation of the progression of glaucomatous damage. Our hypothesis is that glaucoma causes thinning of the nerve fiber layer, and that the earliest stages of that thinning are not detectable by current technology, but are detectable by Optical Coherence Tomography (OCT). OCT is a new technology that we have developed that makes possible the noninvasive, noncontact, cross-sectional tomographic imaging of microstructure in biological tissues. The aim of our research program is to apply this state of the art optical measurement technology for performing micron scale tomographic imaging. OCT is analogous to ultrasound B mode imaging, except that it performs optical ranging and imaging using low coherence optical interferometry with an axial resolution on the order of 10 mum. A transverse sequence of longitudinal optical ranging measurements are used to construct a false color tomographic image of tissue microstructure. Our specific aims are (1) to quantify nerve fiber layer (NFL) thickness in normal humans, glaucoma suspects and early and late glaucoma using OCT, (2) to verify the reproducibility of OCT NFL measurements in vivo in humans, (3) to demonstrate longitudinal changes in NFL thickness in the laser induced glaucoma monkey model, and to correlate NFL thickness as measured in this model with histologic measurements of NFL thickness, and (4) to identify longitudinal changes in NFL thickness in normal humans, in glaucoma suspects, and in early and late glaucoma. This program is constructed to permit cross-sectional population studies of nerve fiber layer thickness in normal and glaucomatous eyes, stratified by age, verification of the reproducibility of these measurements, longitudinal assessment of changes in nerve fiber layer thickness in an animal glaucoma model and longitudinal analysis of changes in nerve fiber layer thickness in normal and glaucomatous human eyes, again stratified by age. Taken together, these studies form an integrated program to investigate the nerve fiber layer in normal and glaucomatous eyes, applying a new technique for optical assessment of microstructure. OCT can perform noninvasive measurement of microstructure with 10mum or higher resolution. This technique has the potential to provide a significant advance in the diagnosis and management of glaucoma. This research plan is developed in accordance with the objectives stated in the Glaucoma Panel's report in the National Eye Institute's National Plan, "[t] to develop clinically relevant and reproducible diagnostic criteria for glaucoma and its progression...[t]o develop reliable structural measurements of optic nerve and nerve fiber layer in glaucoma in order to monitor the status of optic nerve function." In addition, with regard to "image analysis techniques...to provide sensitive measures of optic nerve or nerve fiber layer damage," the National Plan states, "[f]urther refinement is needed" [National Institutes of Health 1994].